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Comparison of First-Line Radiosurgery for Small-Cell and Non-Small Cell Lung Cancer Brain Metastases (Cross-FIRE)

Rusthoven, Chad G; Staley, Alyse W; Gao, Dexiang; Yomo, Shoji; Bernhardt, Denise; Wandrey, Narine; El Shafie, Rami; Kraemer, Anna; Padilla, Oscar; Chiang, Veronica; Faramand, Andrew M; Palmer, Joshua D; Zacharia, Brad E; Wegner, Rodney E; Hattangadi-Gluth, Jona A; Levy, Antonin; Bernstein, Kenneth; Mathieu, David; Cagney, Daniel N; Chan, Michael D; Grills, Inga S; Braunstein, Steve; Lee, Cheng-Chia; Sheehan, Jason P; Kluwe, Christien; Patel, Samir; Halasz, Lia M; Andratschke, Nicolaus; Deibert, Christopher P; Verma, Vivek; Trifiletti, Daniel M; Cifarelli, Christopher P; Debus, Jürgen; Combs, Stephanie E; Sato, Yasunori; Higuchi, Yoshinori; Aoyagi, Kyoko; Brown, Paul D; Alami, Vida; Niranjan, Ajay; Lunsford, L Dade; Kondziolka, Douglas; Camidge, D Ross; Kavanagh, Brian D; Robin, Tyler P; Serizawa, Toru; Yamamoto, Masaaki
INTRODUCTION/BACKGROUND:Historical reservations regarding radiosurgery (SRS) for small-cell-lung-cancer (SCLC) brain metastases (BrM) include concerns for short-interval/diffuse CNS-progression, poor prognoses, and increased neurological mortality specific to SCLC histology. We compared SRS outcomes for SCLC and non-small-cell-lung-cancer (NSCLC) where SRS is well established. METHODS:Multicenter first-line SRS outcomes for SCLC and NSCLC from 2000-2022 were retrospectively collected (N=892-SCLC/N=4,785-NSCLC). Data from the prospective JLGK0901 SRS trial were analyzed as a comparison cohort (N=98-SCLC/N=794-NSCLC). OS and CNS-progression were analyzed using Cox-Proportional-Hazard and Fine-Gray models, respectively, with multivariable (MV) adjustment (including age/sex/performance-status/year/extracranial disease/BrM-number/BrM-volume). Mutation-stratified analyses were performed in propensity score-matched (PSM) retrospective cohorts of EGFR/ALK-positive-NSCLC, mutation-negative-NSCLC, and SCLC. RESULTS:OS was superior with NSCLC over SCLC in the retrospective dataset (median-OS, 10.5 vs 8.6 months, MV-p<0.001) and JLGK0901. Hazard estimates for first CNS-progression favoring NSCLC were similar in both datasets but reached significance in the retrospective dataset only (MV-HR:0.82 [95%-CI:0.73-0.92], p=0.001). In the PSM cohorts, there were continued OS advantages for NSCLC (median-OS, 23.7 [EGFR/ALK-positive-NSCLC] vs 13.6 [mutation-negative-NSCLC] vs 10.4 months [SCLC], pairwise-p-values<0.001), but no significant differences in CNS-progression. Neurological mortality and number of lesions at CNS-progression were similar for NSCLC and SCLC patients. Leptomeningeal-progression was increased in NSCLC patients in the retrospective dataset only (MV-HR:1.61 [95%-CI:1.14-2.26], p=0.007). CONCLUSION/CONCLUSIONS:After SRS, SCLC was associated with shorter OS compared to NSCLC. CNS progression occurred earlier in SCLC overall but was similar in patients matched on baseline characteristics. Neurological mortality, lesions at CNS-progression, and leptomeningeal-progression were comparable. These findings may better inform clinical decision-making for SCLC patients.
PMID: 37142267
ISSN: 1460-2105
CID: 5509152

Stratifying Risk of Future Growth Among Sporadic Vestibular Schwannomas

Marinelli, John P; Schnurman, Zane; Killeen, Daniel E; Nassiri, Ashley M; Hunter, Jacob B; Lees, Katherine A; Lohse, Christine M; Roland, J Thomas; Golfinos, John G; Kondziolka, Douglas; Link, Michael J; Carlson, Matthew L
OBJECTIVE:In certain cases, clinicians may consider continued observation of a vestibular schwannoma after initial growth is detected. The aim of the current work was to determine if patients with growing sporadic vestibular schwannomas could be stratified by the likelihood of subsequent growth based on initial growth behavior. STUDY DESIGN/METHODS:Slice-by-slice volumetric tumor measurements from 3,505 serial magnetic resonance imaging studies were analyzed from 952 consecutively treated patients. SETTING/METHODS:Three tertiary-referral centers. PATIENTS/METHODS:Adults with sporadic vestibular schwannoma. INTERVENTIONS/METHODS:Wait-and-scan. MAIN OUTCOME MEASURES/METHODS:Composite end point of subsequent growth- or treatment-free survival rates, where growth is defined as an additional increase of at least 20% in tumor volume from the volume at the time of initial growth. RESULTS:Among 405 patients who elected continued observation despite documented growth, stratification, of volumetric growth rate into less than 25% (reference: n = 107), 25 to less than 50% (hazard ratio [HR], 1.39; p = 0.06; n = 96), 50 to less than 100% (HR, 1.71; p = 0.002; n = 112), and at least 100% (HR, 2.01; p < 0.001; n = 90) change per year predicted the likelihood of future growth or treatment. Subsequent growth- or treatment-free survival rates (95% confidence interval) at year 5 after detection of initial growth were 31% (21-44%) for those with less than 25% growth per year, 18% (10-32%) for those with 25 to less than 50%, 15% (9-26%) for those with 50 to less than 100%, and 6% (2-16%) for those with at least 100%. Neither patient age ( p = 0.15) nor tumor volume at diagnosis ( p = 0.95) significantly differed across stratification groups. CONCLUSIONS:At the time of diagnosis, clinical features cannot consistently predict which tumors will ultimately display aggressive behavior. Stratification by volumetric growth rate at the time of initial growth results in a stepwise progression of increasing likelihood of subsequent growth. When considering continued observation after initial growth detection, almost 95% of patients who have tumors that double in volume between diagnosis and the first detection of growth demonstrate further tumor growth or undergo treatment if observed to 5 years.
PMID: 37367632
ISSN: 1537-4505
CID: 5535172

Outcome Evaluation of Repeat Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations

Mantziaris, Georgios; Pikis, Stylianos; Dumot, Chloe; Dayawansa, Samantha; Liščák, Roman; May, Jaromir; Lee, Cheng-Chia; Yang, Huai-Che; Martinez Moreno, Nuria; Martinez Álvarez, Roberto; Lunsford, L Dade; Niranjan, Ajay; Wei, Zhishuo; Srinivasan, Priyanka; Tang, Lilly W; Nabeel, Ahmed M; Reda, Wael A; Tawadros, Sameh R; Abdelkarim, Khaled; El-Shehaby, Amr M N; Emad, Reem M; Hesham Elazzazi, Ahmed; Peker, Selcuk; Samanci, Yavuz; Padmanaban, Varun; Jareczek, Francis J; McInerney, James; Cockroft, Kevin M; Mathieu, David; Aldakhil, Salman; Alzate, Juan Diego; Kondziolka, Douglas; Tripathi, Manjul; Palmer, Joshua D; Upadhyay, Rituraj; Lin, Michelle; Zada, Gabriel; Yu, Cheng; Cifarelli, Christopher P; Cifarelli, Daniel T; Xu, Zhiyuan; Sheehan, Jason P
BACKGROUND:Repeat stereotactic radiosurgery (SRS) for persistent cerebral arteriovenous malformation (AVM) has generally favorable patient outcomes. However, reporting studies are limited by small patient numbers and single-institution biases. The purpose of this study was to provide the combined experience of multiple centers, in an effort to fully define the role of repeat SRS for patients with arteriovenous malformation. METHODS:This multicenter, retrospective cohort study included patients treated with repeat, single-fraction SRS between 1987 and 2022. Follow-up began at repeat SRS. The primary outcome was a favorable patient outcome, defined as a composite of nidus obliteration in the absence of hemorrhage or radiation-induced neurological deterioration. Secondary outcomes were obliteration, hemorrhage risk, and symptomatic radiation-induced changes. Competing risk analysis was performed to compute yearly rates and identify predictors for each outcome. RESULTS:<0.001) were associated with reduced probability of favorable outcome. CONCLUSIONS:Repeat SRS confers reasonable obliteration rates with a low complication risk. With most complications occurring in the first 3 years, extending the latency period to 5 years generally increases the rate of favorable patient outcomes and reduces the necessity of a third intervention.
PMID: 37350270
ISSN: 1524-4628
CID: 5542932

Concurrent administration of immune checkpoint inhibitors and single fraction stereotactic radiosurgery in patients with non-small cell lung cancer, melanoma, and renal cell carcinoma brain metastases is not associated with an increased risk of radiation necrosis over non-concurrent treatment: An international multicenter study of 657 patients

Lehrer, Eric J; Kowalchuk, Roman O; Gurewitz, Jason; Bernstein, Kenneth; Kondziolka, Douglas; Niranjan, Ajay; Wei, Zhishuo; Lunsford, L Dade; Fakhoury, Kareem R; Rusthoven, Chad G; Mathieu, David; Trudel, Claire; Malouff, Timothy D; Ruiz-Garcia, Henry; Bonney, Phillip; Hwang, Lindsay; Yu, Cheng; Zada, Gabriel; Patel, Samir; Deibert, Christopher P; Picozzi, Piero; Franzini, Andrea; Attuati, Luca; Prasad, Rahul N; Raval, Raju R; Palmer, Joshua D; Lee, Cheng-Chia; Yang, Huai-Che; Harmsen, William S; Jones, Brianna M; Sharma, Sonam; Ahluwalia, Manmeet S; Sheehan, Jason P; Trifiletti, Daniel M
INTRODUCTION/BACKGROUND:Stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICI) are highly effective treatments for brain metastases, particularly when these therapies are administered concurrently. However, there are limited data reporting the risk of radiation necrosis (RN) in this setting. METHODS:Patients with brain metastases from primary non-small cell lung cancer, renal cell carcinoma, or melanoma treated with SRS and ICI were considered. Time-to-event analyses were conducted for any grade RN and symptomatic RN (SRN) with death incorporated as a competing risk. Additionally, as a secondary analysis, recursive partitioning analysis (RPA) was utilized for model development, and a loop of potential models was analyzed, with the highest-fidelity model selected. Brain V12 Gy thresholds identified on RPA were then incorporated into the competing risks analysis. RESULTS:) (p = < 0.001). There were no statistically significant differences in rates of any grade RN or SRN when accounting for concurrent versus non-concurrent therapy for all patients and by V12 risk groups identified on RPA. CONCLUSION/CONCLUSIONS:Utilization of SRS and ICI results in a low risk of RN and SRN and is not increased with concurrent administration. Therefore, ICI can safely be administered within 4-weeks of SRS. Three risk groups based on V12 Gy were identified, which clinicians may consider to further reduce rates of RN.
PMID: 36690161
ISSN: 1879-355x
CID: 5419502

Epilepsy associated with cerebral cavernous malformations managed with stereotactic radiosurgery: an international, multicenter study

Dumot, Chloe; Mantziaris, Georgios; Pikis, Stylianos; Dayawansa, Sam; Xu, Zhiyuan; Samanci, Yavuz; Ardor, Gokce D; Peker, Selcuk; Nabeel, Ahmed M; Reda, Wael A; Tawadros, Sameh R; Abdel Karim, Khaled; El-Shehaby, Amr M N; Eldin, Reem M Emad; Elazzazi, Ahmed H; Moreno, Nuria Martínez; Álvarez, Roberto Martínez; Liscak, Roman; May, Jaromir; Mathieu, David; Tourigny, Jean-Nicolas; Tripathi, Manjul; Rajput, Akshay; Kumar, Narendra; Kaur, Rupinder; Picozzi, Piero; Franzini, Andrea; Speckter, Herwin; Hernandez, Wenceslao; Brito, Anderson; Warnick, Ronald E; Alzate, Juan; Kondziolka, Douglas; Bowden, Greg N; Patel, Samir; Sheehan, Jason P
OBJECTIVE:Stereotactic radiosurgery (SRS) has been proposed as an alternative to resection for epilepsy control in patients with cerebral cavernous malformations (CCM) located in critical areas. METHODS:This multicentric, retrospective study evaluated seizure control in patients with a solitary CCM and a history of at least one seizure prior to SRS. RESULTS:109 patients (median age at diagnosis 28.9 years, interquartile range (IQR) 16.4 years] were included. Prior to SRS, 2 (1.8%) were seizure-free without medication, 35 (32.1%) were seizure-free with antiseizure medications (ASM), 17 (15.6%) experienced an improvement of at least 50% in seizure frequency/intensity with ASM, and 55 (50.5%) experienced an improvement of less than 50% in seizure frequency/intensity with ASM. At a median follow-up of 3.5 years post-SRS (IQR: 4.9), 52 (47.7%) patients were Engel class I, 13 (11.9%) class II, 17 (15.6%) class III, 22 (20.2%) class IVA or IVB and 5 (4.6%) class IVC. For the 72 patients who had seizures despite medication prior to SRS, a delay > 1.5 years between epilepsy presentation and SRS decreased the probability to become seizure-free, HR 0.25 (95% CI 0.09-0.66), p = 0.006. The probability of achieving Engel I at the last follow-up was 23.6 (95% CI 12.7-33.1) and 31.3% (95% CI 19.3-50.8) at 2 and 5 years respectively. 27 patients were considered as having drug-resistant epilepsy. At a median follow-up of 3.1 years (IQR: 4.7), 6 (22.2%) of them were Engel I, 3 (11.1%) Engel II, 7 (25.9%) Engel III, 8 (29.6%) Engel IVA or IVB and 3 (11.1%) Engel IVC. INTERPRETATION/CONCLUSIONS:47.7% of patients managed with SRS for solitary CCM presenting with seizures achieved Engel class I at the last follow-up.
PMID: 37405688
ISSN: 1432-1459
CID: 5539222

Extended Survival in Patients With Non-Small-Cell Lung Cancer-Associated Brain Metastases in the Modern Era

Berger, Assaf; Mullen, Reed; Bernstein, Kenneth; Alzate, Juan Diego; Silverman, Joshua S; Sulman, Erik P; Donahue, Bernadine R; Chachoua, Abraham; Shum, Elaine; Velcheti, Vamsidhar; Sabari, Joshua; Golfinos, John G; Kondziolka, Douglas
BACKGROUND:Brain metastases (BM) have long been considered a terminal diagnosis with management mainly aimed at palliation and little hope for extended survival. Use of brain stereotactic radiosurgery (SRS) and/or resection, in addition to novel systemic therapies, has enabled improvements in overall and progression-free (PFS) survival. OBJECTIVE:To explore the possibility of extended survival in patients with non-small-cell lung cancer (NSCLC) BM in the current era. METHODS:During the years 2008 to 2020, 606 patients with NSCLC underwent their first Gamma Knife SRS for BM at our institution with point-of-care data collection. We reviewed clinical, molecular, imaging, and treatment parameters to explore the relationship of such factors with survival. RESULTS:The median overall survival was 17 months (95% CI, 13-40). Predictors of increased survival in a multivariable analysis included age <65 years (P < .001), KPS ≥80 (P < .001), absence of extracranial metastases (P < .001), fewer BM at first SRS (≤3, P = .003), and targeted therapy (P = .005), whereas chemotherapy alone was associated with shorter survival (P = .04). In a subgroup of patients managed before 2016 (n = 264), 38 (14%) were long-term survivors (≥5 years), of which 16% required no active cancer treatment (systemic or brain) for ≥3 years by the end of their follow-up. CONCLUSION/CONCLUSIONS:Long-term survival in patients with brain metastases from NSCLC is feasible in the current era of SRS when combined with the use of effective targeted therapeutics. Of those living ≥5 years, the chance for living with stable disease without the need for active treatment for ≥3 years was 16%.
PMID: 36722962
ISSN: 1524-4040
CID: 5420082

Health system-scale language models are all-purpose prediction engines

Jiang, Lavender Yao; Liu, Xujin Chris; Nejatian, Nima Pour; Nasir-Moin, Mustafa; Wang, Duo; Abidin, Anas; Eaton, Kevin; Riina, Howard Antony; Laufer, Ilya; Punjabi, Paawan; Miceli, Madeline; Kim, Nora C; Orillac, Cordelia; Schnurman, Zane; Livia, Christopher; Weiss, Hannah; Kurland, David; Neifert, Sean; Dastagirzada, Yosef; Kondziolka, Douglas; Cheung, Alexander T M; Yang, Grace; Cao, Ming; Flores, Mona; Costa, Anthony B; Aphinyanaphongs, Yindalon; Cho, Kyunghyun; Oermann, Eric Karl
Physicians make critical time-constrained decisions every day. Clinical predictive models can help physicians and administrators make decisions by forecasting clinical and operational events. Existing structured data-based clinical predictive models have limited use in everyday practice owing to complexity in data processing, as well as model development and deployment1-3. Here we show that unstructured clinical notes from the electronic health record can enable the training of clinical language models, which can be used as all-purpose clinical predictive engines with low-resistance development and deployment. Our approach leverages recent advances in natural language processing4,5 to train a large language model for medical language (NYUTron) and subsequently fine-tune it across a wide range of clinical and operational predictive tasks. We evaluated our approach within our health system for five such tasks: 30-day all-cause readmission prediction, in-hospital mortality prediction, comorbidity index prediction, length of stay prediction, and insurance denial prediction. We show that NYUTron has an area under the curve (AUC) of 78.7-94.9%, with an improvement of 5.36-14.7% in the AUC compared with traditional models. We additionally demonstrate the benefits of pretraining with clinical text, the potential for increasing generalizability to different sites through fine-tuning and the full deployment of our system in a prospective, single-arm trial. These results show the potential for using clinical language models in medicine to read alongside physicians and provide guidance at the point of care.
PMID: 37286606
ISSN: 1476-4687
CID: 5536672

Carbon fiber-reinforced PEEK spinal implants for primary and metastatic spine tumors: a systematic review on implant complications and radiotherapy benefits

Khan, Hammad A; Ber, Roee; Neifert, Sean N; Kurland, David B; Laufer, Ilya; Kondziolka, Douglas; Chhabra, Arpit; Frempong-Boadu, Anthony K; Lau, Darryl
OBJECTIVE:By minimizing imaging artifact and particle scatter, carbon fiber-reinforced polyetheretherketone (CF-PEEK) spinal implants are hypothesized to enhance radiotherapy (RT) planning/dosing and improve oncological outcomes. However, robust clinical studies comparing tumor surgery outcomes between CF-PEEK and traditional metallic implants are lacking. In this paper, the authors performed a systematic review of the literature with the aim to describe clinical outcomes in patients with spine tumors who received CF-PEEK implants, focusing on implant-related complications and oncological outcomes. METHODS:A systematic review of the literature published between database inception and May 2022 was performed in accordance with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The PubMed database was queried using the terms "carbon fiber" and "spine" or "spinal." The inclusion criteria were articles that described patients with CF-PEEK pedicle screw fixation and had a minimum of 5 patients. Case reports and phantom studies were excluded. RESULTS:This review included 11 articles with 326 patients (237 with CF-PEEK-based implants and 89 with titanium-based implants). The mean follow-up period was 13.5 months, and most tumors were metastatic (67.1%). The rates of implant-related complications in the CF-PEEK and titanium groups were 7.8% and 4.7%, respectively. The rate of pedicle screw fracture was 1.7% in the CF-PEEK group and 2.4% in the titanium group. The rates of reoperation were 5.7% (with 60.0% because of implant failure or junctional kyphosis) and 4.8% (all because of implant failure or junctional kyphosis) in the CF-PEEK and titanium groups, respectively. When reported, 72.5% of patients received postoperative RT (41.0% stereotactic body RT, 30.8% fractionated RT, 25.6% proton, 2.6% carbon ion). Four articles suggested that implant artifact was reduced in the CF-PEEK group. Local recurrence occurred in 14.4% of CF-PEEK and 10.7% of titanium-implanted patients. CONCLUSIONS:While CF-PEEK harbors similar implant failure rates to traditional metallic implants with reduced imaging artifact, it remains unclear whether CF-PEEK implants improve oncological outcomes. This study highlights the need for prospective, direct comparative clinical studies.
PMID: 37382293
ISSN: 1547-5646
CID: 5540372

Developing an Automated Registry (Autoregistry) of Spine Surgery Using Natural Language Processing and Health System Scale Databases

Cheung, Alexander T M; Kurland, David B; Neifert, Sean; Mandelberg, Nataniel; Nasir-Moin, Mustafa; Laufer, Ilya; Pacione, Donato; Lau, Darryl; Frempong-Boadu, Anthony K; Kondziolka, Douglas; Golfinos, John G; Oermann, Eric Karl
BACKGROUND AND OBJECTIVES/OBJECTIVE:Clinical registries are critical for modern surgery and underpin outcomes research, device monitoring, and trial development. However, existing approaches to registry construction are labor-intensive, costly, and prone to manual error. Natural language processing techniques combined with electronic health record (EHR) data sets can theoretically automate the construction and maintenance of registries. Our aim was to automate the generation of a spine surgery registry at an academic medical center using regular expression (regex) classifiers developed by neurosurgeons to combine domain expertise with interpretable algorithms. METHODS:We used a Hadoop data lake consisting of all the information generated by an academic medical center. Using this database and structured query language queries, we retrieved every operative note written in the department of neurosurgery since our transition to EHR. Notes were parsed using regex classifiers and compared with a random subset of 100 manually reviewed notes. RESULTS:A total of 31 502 operative cases were downloaded and processed using regex classifiers. The codebase required 5 days of development, 3 weeks of validation, and less than 1 hour for the software to generate the autoregistry. Regex classifiers had an average accuracy of 98.86% at identifying both spinal procedures and the relevant vertebral levels, and it correctly identified the entire list of defined surgical procedures in 89% of patients. We were able to identify patients who required additional operations within 30 days to monitor outcomes and quality metrics. CONCLUSION/CONCLUSIONS:This study demonstrates the feasibility of automatically generating a spine registry using the EHR and an interpretable, customizable natural language processing algorithm which may reduce pitfalls associated with manual registry development and facilitate rapid clinical research.
PMID: 37345933
ISSN: 1524-4040
CID: 5542832

Augmented Reality-Assisted Percutaneous Rhizotomy for Trigeminal Neuralgia

Berger, Assaf; Choudhry, Osamah J; Kondziolka, Douglas
BACKGROUND:Percutaneous rhizotomy of the trigeminal nerve is a common surgery to manage medically refractory trigeminal neuralgia. Traditionally, these procedures have been performed based on anatomic landmarks with fluoroscopic guidance. Augmented reality (AR) relays virtual content on the real world and has the potential to improve localization of surgical targets based on preoperative imaging. OBJECTIVE:To study the potential application and benefits of AR as an adjunct to traditional fluoroscopy-guided glycerol rhizotomy (GR). METHODS:We used traditional fluoroscopy-guided percutaneous GR technique as previously described, performed under general anesthesia. Anatomic registration to the Medivis SurgicalAR system was performed based on the patient's preoperative computerized tomography, and the surgeon was equipped with the system's AR goggles. AR was used as an adjunct to fluoroscopy for trajectory planning to place a spinal needle into the medial aspect of the foramen ovale. RESULTS:A 50-year-old woman with multiple sclerosis-related right-sided classical trigeminal neuralgia had persistent pain, refractory to medications, previous gamma knife stereotactic radiosurgery, and percutaneous radiofrequency rhizotomy performed elsewhere. The patient underwent AR-assisted fluoroscopy-guided percutaneous GR. The needle was placed into the right trigeminal cistern within seconds. She was discharged home after a few hours of observation with no complications and reported pain relief. CONCLUSION/CONCLUSIONS:AR-assisted percutaneous rhizotomy may enhance the learning curve of these types of procedures and decrease surgery duration and radiation exposure. This allowed rapid and correct placement of a spinal needle through the foramen ovale.
PMID: 36815787
ISSN: 2332-4260
CID: 5433982